Heme oxygenase 1 controls early innate immune response of macrophages to Salmonella Typhimurium infection

Cellular Microbiology

Volumn 18, Issue 10, 2016, Pages 1374-1389

  Mitterstiller, Anna Maria ^a   Haschka, David ^a   Dichtl, Stefanie ^a   Nairz, Manfred ^a   Demetz, Egon ^a   Talasz, Heribert ^a   Soares, Miguel P ^c   Einwallner, Elisa ^d   Esterbauer, Harald ^d   Fang, Ferric C ^b   Geley, Stephan ^a   Weiss, Guenter ^a  

^a INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^b UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^c INSTITUTO GULBENKIAN DE CIÊNCIA   (Portugal)

^d MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

BILIVERDIN; HEME OXYGENASE 1; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; IRON; NITROGEN; REACTIVE OXYGEN METABOLITE; SHORT HAIRPIN RNA; TUMOR NECROSIS FACTOR;

ANIMAL CELL; ARTICLE; BACTERIAL GROWTH; BACTERIAL SURVIVAL; CONTROLLED STUDY; ENZYME INHIBITION; GENETIC TRANSCRIPTION; INNATE IMMUNITY; MACROPHAGE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SALMONELLA ENTERICA SEROVAR TYPHIMURIUM; SALMONELLOSIS;

EID: 84987850141     PISSN: 14625814     EISSN: 14625822     Source Type: Journal    
DOI: 10.1111/cmi.12578     Document Type: Article

References (94)

1. Abdalla, M.Y., Ahmad, I.M., Switzer, B., and Britigan, B.E. (2015) Induction of heme oxygenase-1 contributes to survival of Mycobacterium abscessus in human macrophages-like THP-1 cells. Redox Biol 4: 328–339.
2. Ables, G.P., Takamatsu, D., Noma, H., El-Shazly, S., Jin, H.K., Taniguchi, T., et al. (2001) The roles of Nramp1 and Tnfa genes in nitric oxide production and their effect on the growth of Salmonella typhimurium in macrophages from Nramp1 congenic and tumor necrosis factor-alpha−/− mice. J Interferon cytokine Res: Off J Int Soc Interferon Cytokine Res 21: 53–62.
3. Andrews-Polymenis, H.L., Baumler, A.J., McCormick, B.A., and Fang, F.C. (2010) Taming the elephant: Salmonella biology, pathogenesis, and prevention. Infect Immun 78: 2356–2369.
4. Arezes, J., Jung, G., Gabayan, V., Valore, E., Ruchala, P., Gulig, P.A., et al. (2015) Hepcidin-induced hypoferremia is a critical host defense mechanism against the siderophilic bacterium Vibrio vulnificus. Cell Host Microbe 17: 47–57.
5. Armitage, A.E., Eddowes, L.A., Gileadi, U., Cole, S., Spottiswoode, N., Selvakumar, T.A., et al. (2011) Hepcidin regulation by innate immune and infectious stimuli. Blood 118: 4129–4139.
6. Bao, G., Clifton, M., Hoette, T.M., Mori, K., Deng, S.X., Qiu, A., et al. (2010) Iron traffics in circulation bound to a siderocalin (Ngal)-catechol complex. Nat Chem Biol 6: 602–609.
7. Bellmann-Weiler, R., Martinz, V., Kurz, K., Engl, S., Feistritzer, C., Fuchs, D., et al. (2010) Divergent modulation of Chlamydia pneumoniae infection cycle in human monocytic and endothelial cells by iron, tryptophan availability and interferon gamma. Immunobiology 215: 842–848.
8. Berger, T., Togawa, A., Duncan, G.S., Elia, A.J., You-Ten, A., Wakeham, A., et al. (2006) Lipocalin 2-deficient mice exhibit increased sensitivity to Escherichia coli infection but not to ischemia-reperfusion injury. Proc Natl Acad Sci U S A 103: 1834–1839.
9. Bogdan, C. (2001) Nitric oxide and the immune response. Nat Immunol 2: 907–916.
10. Cassat, J.E., and Skaar, E.P. (2013) Iron in infection and immunity. Cell Host Microbe 13: 509–519.
11. Cellier, M.F., Courville, P., and Campion, C. (2007) Nramp1 phagocyte intracellular metal withdrawal defense. Microbes Infection/Institut Pasteur 9: 1662–1670.
12. Chlosta, S., Fishman, D.S., Harrington, L., Johnson, E.E., Knutson, M.D., Wessling-Resnick, M., and Cherayil, B.J. (2006) The iron efflux protein ferroportin regulates the intracellular growth of Salmonella enterica. Infect Immun 74: 3065–3067.
13. Chung, S.W., Liu, X., Macias, A.A., Baron, R.M., and Perrella, M.A. (2008) Heme oxygenase-1-derived carbon monoxide enhances the host defense response to microbial sepsis in mice. J Clin Invest 118: 239–247.
14. Crouch, M.L., Castor, M., Karlinsey, J.E., Kalhorn, T., and Fang, F.C. (2008) Biosynthesis and IroC-dependent export of the siderophore salmochelin are essential for virulence of Salmonella enterica serovar Typhimurium. Mol Microbiol 67: 971–983.
15. Cunnington, A.J., de Souza, J.B., Walther, M., and Riley, E.M. (2012) Malaria impairs resistance to Salmonella through heme- and heme oxygenase-dependent dysfunctional granulocyte mobilization. Nat Med 18: 120–127.
16. Desmard, M., Davidge, K.S., Bouvet, O., Morin, D., Roux, D., Foresti, R., et al. (2009) A carbon monoxide-releasing molecule (CORM-3) exerts bactericidal activity against Pseudomonas aeruginosa and improves survival in an animal model of bacteraemia. FASEB J: Off Pub Fed Am Soc Experiment Biol 23: 1023–1031.
17. DiDonato, J.A., Mercurio, F., and Karin, M. (2012) NF-kappaB and the link between inflammation and cancer. Immunol Rev 246: 379–400.
18. Drakesmith, H., and Prentice, A.M. (2012) Hepcidin and the iron-infection axis. Science 338: 768–772.
19. Evstatiev, R., and Gasche, C. (2012) Iron sensing and signalling. Gut 61: 933–952.
20. Fang, F.C., and Weiss, G. (2014) Iron ERRs with Salmonella. Cell Host Microbe 15: 515–516.
21. Ferris, C.D., Jaffrey, S.R., Sawa, A., Takahashi, M., Brady, S.D., Barrow, R.K., et al. (1999) Haem oxygenase-1 prevents cell death by regulating cellular iron. Nat Cell Biol 1: 152–157.
22. Flo, T.H., Smith, K.D., Sato, S., Rodriguez, D.J., Holmes, M.A., Strong, R.K., et al. (2004) Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 432: 917–921.
23. Frawley, E.R., Crouch, M.L., Bingham-Ramos, L.K., Robbins, H.F., Wang, W., Wright, G.D., and Fang, F.C. (2013) Iron and citrate export by a major facilitator superfamily pump regulates metabolism and stress resistance in Salmonella Typhimurium. Proc Natl Acad Sci U S A 110: 12054–12059.
24. Fritsche, G., Nairz, M., Libby, S.J., Fang, F.C., and Weiss, G. (2012) Slc11a1 (Nramp1) impairs growth of Salmonella enterica serovar typhimurium in macrophages via stimulation of lipocalin-2 expression. J Leukoc Biol 92: 353–359.
25. Ganz, T. (2009) Iron in innate immunity: starve the invaders. Curr Opin Immunol 21: 63–67.
26. Gloire, G., Legrand-Poels, S., and Piette, J. (2006) NF-kappaB activation by reactive oxygen species: fifteen years later. Biochem Pharmacol 72: 1493–1505.
27. Gozzelino, R., Andrade, B.B., Larsen, R., Luz, N.F., Vanoaica, L., Seixas, E., et al. (2012) Metabolic adaptation to tissue iron overload confers tolerance to malaria. Cell Host Microbe 12: 693–704.
28. Gozzelino, R., Jeney, V., and Soares, M.P. (2010) Mechanisms of cell protection by heme oxygenase-1. Annu Rev Pharmacol Toxicol 50: 323–354.
29. Haschka, D., Nairz, M., Demetz, E., Wienerroither, S., Decker, T., and Weiss, G. (2015) Contrasting regulation of macrophage iron homeostasis in response to infection with Listeria monocytogenes depending on localization of bacteria. Metallomics: Integr Biometal Sci 7: 1036–1045.
30. Hegazi, R.A., Rao, K.N., Mayle, A., Sepulveda, A.R., Otterbein, L.E., and Plevy, S.E. (2005) Carbon monoxide ameliorates chronic murine colitis through a heme oxygenase 1-dependent pathway. J Exp Med 202: 1703–1713.
31. Hentze, M.W., Muckenthaler, M.U., Galy, B., and Camaschella, C. (2010) Two to tango: regulation of mammalian iron metabolism. Cell 142: 24–38.
32. Jais, A., Einwallner, E., Sharif, O., Gossens, K., Lu, T.T., Soyal, S.M., et al. (2014) Heme oxygenase-1 drives metaflammation and insulin resistance in mouse and man. Cell 158: 25–40.
33. Kaplan, J. (2002) Mechanisms of cellular iron acquisition: another iron in the fire. Cell 111: 603–606.
34. Karin, M., and Greten, F.R. (2005) NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 5: 749–759.
35. Lahiri, A., Lahiri, A., Iyer, N., Das, P., and Chakravortty, D. (2010) Visiting the cell biology of Salmonella infection. Microbes Infection/Institut Pasteur 12: 809–818.
36. Larsen, R., Gozzelino, R., Jeney, V., Tokaji, L., Bozza, F.A., Japiassu, A.M., et al. (2010) A central role for free heme in the pathogenesis of severe sepsis. Sci Transl Med 2: 51ra71.
37. Leung, K.Y., and Finlay, B.B. (1991) Intracellular replication is essential for the virulence of Salmonella typhimurium. Proc Natl Acad Sci U S A 88: 11470–11474.
38. Liu, Z., Reba, S., Chen, W.D., Porwal, S.K., Boom, W.H., Petersen, R.B., et al. (2014) Regulation of mammalian siderophore 2,5-DHBA in the innate immune response to infection. J Exp Med 211: 1197–1213.
39. Ludwiczek, S., Aigner, E., Theurl, I., and Weiss, G. (2003) Cytokine-mediated regulation of iron transport in human monocytic cells. Blood 101: 4148–4154.
40. MacMicking, J., Xie, Q.W., and Nathan, C. (1997) Nitric oxide and macrophage function. Annu Rev Immunol 15: 323–350.
41. Mamiya, T., Katsuoka, F., Hirayama, A., Nakajima, O., Kobayashi, A., Maher, J.M., et al. (2008) Hepatocyte-specific deletion of heme oxygenase-1 disrupts redox homeostasis in basal and oxidative environments. Tohoku J Exp Med 216: 331–339.
42. Mastroeni, P., Vazquez-Torres, A., Fang, F.C., Xu, Y., Khan, S., Hormaeche, C.E., and Dougan, G. (2000) Antimicrobial actions of the NADPH phagocyte oxidase and inducible nitric oxide synthase in experimental salmonellosis. II. Effects on microbial proliferation and host survival in vivo. J Exp Med 192: 237–248.
43. Megias, J., Busserolles, J., and Alcaraz, M.J. (2007) The carbon monoxide-releasing molecule CORM-2 inhibits the inflammatory response induced by cytokines in Caco-2 cells. Br J Pharmacol 150: 977–986.
44. Melillo, G., Taylor, L.S., Brooks, A., Musso, T., Cox, G.W., and Varesio, L. (1997) Functional requirement of the hypoxia-responsive element in the activation of the inducible nitric oxide synthase promoter by the iron chelator desferrioxamine. J Biol Chem 272: 12236–12243.
45. Motterlini, R., Haas, B., and Foresti, R. (2012) Emerging concepts on the anti-inflammatory actions of carbon monoxide-releasing molecules (CO-RMs). Med Gas Res 2: 28.
46. Mulero, V., and Brock, J.H. (1999) Regulation of iron metabolism in murine J774 macrophages: role of nitric oxide-dependent and -independent pathways following activation with gamma interferon and lipopolysaccharide. Blood 94: 2383–2389.
47. Nairz, M., Ferring-Appel, D., Casarrubea, D., Sonnweber, T., Viatte, L., Schroll, A., et al. (2015) Iron regulatory proteins mediate host resistance to Salmonella infection. Cell Host Microbe 18: 254–261.
48. Nairz, M., Haschka, D., Demetz, E., and Weiss, G. (2014) Iron at the interface of immunity and infection. Front Pharmacol 5: 152.
49. Nairz, M., Schleicher, U., Schroll, A., Sonnweber, T., Theurl, I., Ludwiczek, S., et al. (2013) Nitric oxide-mediated regulation of ferroportin-1 controls macrophage iron homeostasis and immune function in Salmonella infection. J Exp Med 210: 855–873.
50. Nairz, M., Schroll, A., Sonnweber, T., and Weiss, G. (2010) The struggle for iron—a metal at the host-pathogen interface. Cell Microbiol 12: 1691–1702.
51. Nairz, M., Theurl, I., Ludwiczek, S., Theurl, M., Mair, S.M., Fritsche, G., and Weiss, G. (2007) The co-ordinated regulation of iron homeostasis in murine macrophages limits the availability of iron for intracellular Salmonella typhimurium. Cell Microbiol 9: 2126–2140.
52. Nairz, M., Theurl, I., Schroll, A., Theurl, M., Fritsche, G., Lindner, E., et al. (2009) Absence of functional Hfe protects mice from invasive Salmonella enterica serovar Typhimurium infection via induction of lipocalin-2. Blood 114: 3642–3651.
53. Nathan, C., and Shiloh, M.U. (2000) Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc Natl Acad Sci U S A 97: 8841–8848.
54. Nemeth, E., Tuttle, M.S., Powelson, J., Vaughn, M.B., Donovan, A., Ward, D.M., et al. (2004) Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306: 2090–2093.
55. Nix, R.N., Altschuler, S.E., Henson, P.M., and Detweiler, C.S. (2007) Hemophagocytic macrophages harbor Salmonella enterica during persistent infection. PLoS Pathog 3: e193.
56. Nobre, L.S., Al-Shahrour, F., Dopazo, J., and Saraiva, L.M. (2009) Exploring the antimicrobial action of a carbon monoxide-releasing compound through whole-genome transcription profiling of Escherichia coli. Microbiology 155: 813–824.
57. Oexle, H., Kaser, A., Most, J., Bellmann-Weiler, R., Werner, E.R., Werner-Felmayer, G., and Weiss, G. (2003) Pathways for the regulation of interferon-gamma-inducible genes by iron in human monocytic cells. J Leukoc Biol 74: 287–294.
58. Olakanmi, O., Schlesinger, L.S., Ahmed, A., and Britigan, B.E. (2002) Intraphagosomal Mycobacterium tuberculosis acquires iron from both extracellular transferrin and intracellular iron pools. Impact of interferon-gamma and hemochromatosis. J Biol Chem 277: 49727–49734.
59. Onyiah, J.C., Sheikh, S.Z., Maharshak, N., Steinbach, E.C., Russo, S.M., Kobayashi, T., et al. (2013) Carbon monoxide and heme oxygenase-1 prevent intestinal inflammation in mice by promoting bacterial clearance. Gastroenterology 144: 789–798.
60. Orozco, L.D., Kapturczak, M.H., Barajas, B., Wang, X., Weinstein, M.M., Wong, J., et al. (2007) Heme oxygenase-1 expression in macrophages plays a beneficial role in atherosclerosis. Circ Res 100: 1703–1711.
61. Otterbein, L.E., Bach, F.H., Alam, J., Soares, M., Tao Lu, H., Wysk, M., et al. (2000) Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 6: 422–428.
62. Pantopoulos, K., Porwal, S.K., Tartakoff, A., and Devireddy, L. (2012) Mechanisms of mammalian iron homeostasis. Biochemistry 51: 5705–5724.
63. Paradkar, P.N., De Domenico, I., Durchfort, N., Zohn, I., Kaplan, J., and Ward, D.M. (2008) Iron depletion limits intracellular bacterial growth in macrophages. Blood 112: 866–874.
64. Rosen, G.M., Pou, S., Ramos, C.L., Cohen, M.S., and Britigan, B.E. (1995) Free radicals and phagocytic cells. Faseb J 9: 200–209.
65. Ryter, S.W., Alam, J., and Choi, A.M. (2006) Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev 86: 583–650.
66. Ryter, S.W., and Tyrrell, R.M. (2000) The heme synthesis and degradation pathways: role in oxidant sensitivity. Heme Oxygenase has both pro- and Antioxidant Properties Free Radical Biol & med 28: 289–309.
67. Sawle, P., Foresti, R., Mann, B.E., Johnson, T.R., Green, C.J., and Motterlini, R. (2005) Carbon monoxide-releasing molecules (CO-RMs) attenuate the inflammatory response elicited by lipopolysaccharide in RAW264.7 murine macrophages. Br J Pharmacol 145: 800–810.
68. Schaible, U.E., and Kaufmann, S.H. (2004) Iron and microbial infection. Nat Rev Microbiol 2: 946–953.
69. Seldon, M.P., Silva, G., Pejanovic, N., Larsen, R., Gregoire, I.P., Filipe, J., et al. (2007) Heme oxygenase-1 inhibits the expression of adhesion molecules associated with endothelial cell activation via inhibition of NF-kappaB RelA phosphorylation at serine 276. J Immunol 179: 7840–7851.
70. Shiloh, M.U., and Nathan, C.F. (2000) Reactive nitrogen intermediates and the pathogenesis of Salmonella and mycobacteria. Curr Opin Microbiol 3: 35–42.
71. Sigl, R., Ploner, C., Shivalingaiah, G., Kofler, R., and Geley, S. (2014) Development of a multipurpose GATEWAY-based lentiviral tetracycline-regulated conditional RNAi system (GLTR). PLoS One 9: e97764.
72. Silva-Gomes, S., Appelberg, R., Larsen, R., Soares, M.P., and Gomes, M.S. (2013) Heme catabolism by heme oxygenase-1 confers host resistance to Mycobacterium infection. Infect Immun 81: 2536–2545.
73. Soares, M.P., and Weiss, G. (2015) The iron age of host–microbe interactions. EMBO Rep 16: 1482–1500.
74. Tak, P.P., and Firestein, G.S. (2001) NF-kappaB: a key role in inflammatory diseases. J Clin Invest 107: 7–11.
75. Tavares, A.F., Teixeira, M., Romao, C.C., Seixas, J.D., Nobre, L.S., and Saraiva, L.M. (2011) Reactive oxygen species mediate bactericidal killing elicited by carbon monoxide-releasing molecules. J Biol Chem 286: 26708–26717.
76. Tenhunen, R., Marver, H.S., and Schmid, R. (1968) The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc Natl Acad Sci U S A 61: 748–755.
77. Theurl, I., Aigner, E., Theurl, M., Nairz, M., Seifert, M., Schroll, A., et al. (2009) Regulation of iron homeostasis in anemia of chronic disease and iron deficiency anemia: diagnostic and therapeutic implications. Blood 113: 5277–5286.
78. Theurl, I., Mattle, V., Seifert, M., Mariani, M., Marth, C., and Weiss, G. (2006) Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease. Blood 107: 4142–4148.
79. Theurl, I., Theurl, M., Seifert, M., Mair, S., Nairz, M., Rumpold, H., et al. (2008) Autocrine formation of hepcidin induces iron retention in human monocytes. Blood 111: 2392–2399.
80. Van Zandt, K.E., Sow, F.B., Florence, W.C., Zwilling, B.S., Satoskar, A.R., Schlesinger, L.S., and Lafuse, W.P. (2008) The iron export protein ferroportin 1 is differentially expressed in mouse macrophage populations and is present in the mycobacterial-containing phagosome. J Leukoc Biol 84: 689–700.
81. Varesio, L., Battaglia, F., Raggi, F., Ledda, B., and Bosco, M.C. (2010) Macrophage-inflammatory protein-3alpha/CCL-20 is transcriptionally induced by the iron chelator desferrioxamine in human mononuclear phagocytes through nuclear factor (NF)-kappaB. Mol Immunol 47: 685–693.
82. Vazquez-Torres, A., Jones-Carson, J., Mastroeni, P., Ischiropoulos, H., and Fang, F.C. (2000) Antimicrobial actions of the NADPH phagocyte oxidase and inducible nitric oxide synthase in experimental salmonellosis. I. Effects on microbial killing by activated peritoneal macrophages in vitro. J Exp Med 192: 227–236.
83. Velayudhan, J., Karlinsey, J.E., Frawley, E.R., Becker, L.A., Nartea, M., and Fang, F.C. (2014) Distinct roles of the Salmonella enterica serovar Typhimurium CyaY and YggX proteins in the biosynthesis and repair of iron–sulfur clusters. Infect Immun 82: 1390–1401.
84. Victor, V.M., Rocha, M., and De la Fuente, M. (2003) Regulation of macrophage function by the antioxidant N-acetylcysteine in mouse-oxidative stress by endotoxin. Int Immunopharmacol 3: 97–106.
85. Wang, X.M., Kim, H.P., Nakahira, K., Ryter, S.W., and Choi, A.M. (2009) The heme oxygenase-1/carbon monoxide pathway suppresses TLR4 signaling by regulating the interaction of TLR4 with caveolin-1. J Immunol 182: 3809–3818.
86. Ward, D.M., and Kaplan, J. (2012) Ferroportin-mediated iron transport: expression and regulation. Biochim Biophys Acta 1823: 1426–1433.
87. Wegiel, B., Hauser, C.J., and Otterbein, L.E. (2015) Heme as a danger molecule in pathogen recognition. Free Radic Biol Med 89: 651–661.
88. Wegiel, B., Larsen, R., Gallo, D., Chin, B.Y., Harris, C., Mannam, P., et al. (2014) Macrophages sense and kill bacteria through carbon monoxide-dependent inflammasome activation. J Clin Invest 124: 4926–4940.
89. Weinberg, E.D. (2009) Iron availability and infection. Biochim Biophys Acta 1790: 600–605.
90. Weiss, G., and Schaible, U.E. (2015) Macrophage defense mechanisms against intracellular bacteria. Immunol Rev 264: 182–203.
91. Weiss, G., Werner-Felmayer, G., Werner, E.R., Grunewald, K., Wachter, H., and Hentze, M.W. (1994) Iron regulates nitric oxide synthase activity by controlling nuclear transcription. J Exp Med 180: 969–976.
92. Wessling-Resnick, M. (2010) Iron homeostasis and the inflammatory response. Annu Rev Nutr 30: 105–122.
93. Yet, S.F., Tian, R., Layne, M.D., Wang, Z.Y., Maemura, K., Solovyeva, M., et al. (2001) Cardiac-specific expression of heme oxygenase-1 protects against ischemia and reperfusion injury in transgenic mice. Circ Res 89: 168–173.
94. Zaki, M.H., Fujii, S., Okamoto, T., Islam, S., Khan, S., Ahmed, K.A., et al. (2009) Cytoprotective function of heme oxygenase 1 induced by a nitrated cyclic nucleotide formed during murine salmonellosis. J Immunol 182: 3746–3756.